System and method for target substance identification

ABSTRACT

Systems and techniques for detecting a target substance, such as THC, in a breath constituent sample are provided.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/217,264, filed on Jul. 22, 2016, and titled “SYSTEM AND METHOD FORTARGET SUBSTANCE IDENTIFICATION,” which issued as U.S. Pat. No.9,933,445, on Apr. 3, 2018, which itself claims benefit of priorityunder 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No.62/337,286, filed May 16, 2016, and titled “BREATH COLLECTOR MODULE,”U.S. Provisional Patent Application No. 62/351,858, filed Jun. 17, 2016,and titled “COMPOSITIONS AND METHODS FOR DETECTION OF TARGET CONSTITUENTIN EXHALED BREATH,” and U.S. Provisional Patent Application No.62/351,821, filed Jun. 17, 2016, and titled “SYSTEM AND METHOD FORTARGET SUBSTANCE IDENTIFICATION”; this application is also related toU.S. patent application Ser. No. 15/217,151, filed Jul. 22, 2016, andtitled “COMPOSITIONS AND METHODS FOR DETECTION OF TARGET CONSTITUENT INEXHALED BREATH,” which also claims benefit of priority to U.S.Provisional Patent Application No. 62/351,858, filed Jun. 17, 2016; thisapplication is also related to U.S. patent application Ser. No.14/997,405, titled “METHOD, DEVICE AND SYSTEM FOR TARGET SUBSTANCEDETECTION” and filed Jan. 15, 2016, which claims priority benefit under35 U.S.C. § 119(e) to U.S. Provisional Application No. 62/104,813, filedJan. 18, 2015, and 62/107,331, filed Jan. 23, 2015, both of which aretitled “METHOD, DEVICE AND SYSTEM FOR TARGET SUBSTANCE DETECTION,” aswell as to U.S. Provisional Application No. 62/277,854, filed Jan. 12,2016, and titled “PORTABLE, HAND-HELD INSTRUMENT FOR DETECTION ANDQUANTIFICATION OF CANNABINOIDS AND ALCOHOL IN EXHALED HUMAN BREATH”; allof these applications are hereby incorporated by reference herein intheir entireties.

FIELD OF THE INVENTION

The present disclosure relates generally to analytical measurementdevices, and more specifically to devices capable of measuringsubstances in exhaled human breath.

BACKGROUND

With legalization of marijuana expanding and the risk ofmarijuana-associated impaired driving increasing, it is anticipated bythe present inventors that there will be an increased need for portableand accurate measurement devices for quantifying levels of cannabinoidcompounds, such as tetrahydrocannabinol (THC), that are present in aperson's breath, e.g., such as during a traffic stop for suspecteddriving-under-the-influence. THC detection poses significant challengessince the amounts of THC that may be present in an exhaled breath arequite minute—much more so than is the case with alcohol. Furthermore,THC detection in human breath is generally the only reliable way todetermine if a suspected marijuana user is under the influence. Unlikewith alcohol, which the body can purge in relatively short order, e.g.,less than a day, THC compounds may be present in a person's body longafter they are no longer under the influence of the THC. Thus, detectionof THC via blood or urine sample may result in false positives. Testingfor THC in breath at the roadside would be convenient, non-invasive, andleverages the wide acceptance of administering a breath test at theroadside, as is commonly employed for alcohol.

SUMMARY

Details of one or more implementations of the subject matter describedin this specification are set forth in the accompanying drawings and thedescription below. Other features, aspects, and advantages will becomeapparent from the description, the drawings, and the claims.

In some implementations, a tetrahydrocannabinol (THC) detection systemis provided that includes an elution port, a sample reservoir containinga sample solvent, an indicator chamber containing an indicator, asolvent reservoir, a buffer reservoir containing a basic buffer, anoptical measurement chamber, and a plurality of valves that areconfigured to control fluid flow from or to the elution port, the samplereservoir, the indicator chamber, the solvent reservoir, and the opticalmeasurement chamber. The plurality of valves may be arranged such thatfluid flow between such components is controllable to permit a breathconstituent sample to be conveyed from the elution port to the samplereservoir, permit at least a portion of the basic buffer to be combinedwith the breath constituent sample, permit at least a first portion ofthe indicator to be combined with the breath constituent sample to forma sample adduct with any THC that is present in the breath constituentsample, permit at least a first portion of the solvent to be combinedwith the sample adduct, and permit the combined sample adduct andsolvent to be delivered to the optical measurement chamber.

In some implementations, the solvent in the solvent reservoir may be amixture of methyl tertiary butyl ether and heptane.

In some implementations of the THC detection system, the system mayfurther include a controller having one or more processors and a memory.The one or more processors may be communicatively connected with thememory, and the memory may store computer-executable instructions forcontrolling the one or more processors to control the plurality ofvalves to facilitate the conveying of the breath constituent sample fromthe elution port to the sample reservoir, the combining of the at leasta first portion of the indicator with the breath constituent sample toform the sample adduct, the combining of the at least a first portion ofthe solvent with the sample adduct, and the delivering of the combinedsample adduct and solvent to the optical measurement chamber.

In some implementations of the THC detection system, the elution port,the sample reservoir, the indicator chamber, the solvent reservoir, theoptical measurement chamber, and the plurality of valves may be locatedin a common cartridge that is configured to be inserted into an analysisunit having an optical sensor system configured to obtain luminescencereadings from the combined sample adduct and solvent from the opticalmeasurement chamber. In some such implementations of the THC detectionsystem, the system may further include an analysis station that isconfigured to receive the common cartridge, includes the optical sensorsystem, and includes actuators configured to independently actuate thesample reservoir and the solvent reservoir so as to drive fluids intoand out of the sample reservoir and the solvent reservoir.

In some implementations of the THC detection system, the plurality ofvalves may be further arranged such that fluid flow between thecomponents is controllable to deliver an eluent from the samplereservoir to the elution port before the breath constituent sample isconveyed to the sample reservoir. In some such implementations, thesystem may further include a handheld breath capture module configuredto removably connect with the elution port, the handheld breath capturemodule including a mouthpiece, a saliva trap, and a catch media locatedbetween the saliva trap and the elution port when the handheld breathcapture module is connected with the elution port. In some further suchimplementations, the catch media may be silica microbeads having nominalmaximum dimensions of between 400 μm and 1500 μm, glass wool, activatedcharcoal granules, glass wool, layered mesh screens, or frits.

In some implementations of the THC detection system, the system mayfurther include a controller having one or more processors and a memory.The one or more processors may be communicatively connected with thememory, and the memory may store computer-executable instructions forcontrolling the one or more processors to control the plurality ofvalves to facilitate the delivering of the eluent from the samplereservoir to the elution port, the conveying of the breath constituentsample from the elution port to the sample reservoir, the combining ofthe at least a first portion of the indicator with the breathconstituent sample to form the sample adduct, the combining of the atleast a first portion of the solvent with the sample adduct, and thedelivering of the combined sample adduct and solvent to the opticalmeasurement chamber.

In some implementations of the THC detection system, the system mayfurther include an activation cell, and the plurality of valves may befurther arranged such that fluid flow between the components iscontrollable to permit the combined sample adduct and solvent to bedelivered to the activation cell prior to delivering the combined sampleadduct and solvent to the optical measurement chamber.

In some implementations of the THC detection system, the system mayfurther include a first calibration sample reservoir and a secondcalibration sample reservoir. In such implementations, the plurality ofvalves may be further arranged such that fluid flow between thecomponents is controllable to permit at least a second portion of theindicator from the indicator chamber to be combined with a firstcalibration sample in the first calibration sample reservoir to form afirst calibration sample adduct with any THC that is present in thefirst calibration sample, permit at least a second portion of thesolvent to be combined with the first calibration sample adduct, permitthe combined first calibration sample adduct and solvent to be deliveredto the optical measurement chamber, permit at least a third portion ofthe indicator from the indicator chamber to be combined with a secondcalibration sample in the second calibration sample reservoir to form asecond calibration sample adduct with any THC that is present in thesecond calibration sample, permit at least a third portion of thesolvent to be combined with the second calibration sample adduct, andpermit the combined second calibration sample adduct and solvent to bedelivered to the optical measurement chamber. In some suchimplementations, the first calibration sample may contain no THC and thesecond calibration sample may contain a known amount of THC. In somealternative such implementations, the first calibration sample maycontain a first known amount of THC and the second calibration samplemay contain a second known amount of THC that is greater than the firstknown amount of THC.

In some implementations of the system, the system may further include acontroller having one or more processors and a memory. In suchimplementations, the one or more processors may be communicativelyconnected with the memory and the memory may store computer-executableinstructions for controlling the one or more processors to control theplurality of valves to facilitate the delivering of the eluent from thesample reservoir to the elution port, the conveying of the breathconstituent sample from the elution port to the sample reservoir, thecombining of the at least a first portion of the indicator with thebreath constituent sample to form the sample adduct, the combining ofthe at least a first portion of the solvent with the sample adduct, thedelivering of the combined sample adduct and solvent to the opticalmeasurement chamber, the combining of the at least a second portion ofthe indicator with the first calibration sample to form the firstcalibration sample adduct, the combining of the at least a secondportion of the solvent with the first calibration sample adduct, thedelivering of the combined first calibration sample adduct and solventto the optical measurement chamber, the combining of the at least athird portion of the indicator with the second calibration sample toform the second calibration sample adduct, the combining of the at leasta third portion of the solvent with the second calibration sampleadduct, and the delivering of the combined second calibration sampleadduct and solvent to the optical measurement chamber.

In some such implementations, the THC detection system may furtherinclude a first activation cell and a second activation cell, and theplurality of valves may be further arranged such that fluid flow betweenthe components is controllable to permit the combined sample adduct andsolvent to be introduced into the first activation cell prior todelivering the combined sample adduct and solvent to the opticalmeasurement chamber and permit the combined second calibration sampleadduct and solvent to be delivered to the second activation cell priorto delivering the combined second calibration sample adduct and solventto the optical measurement chamber.

In some implementations of the THC detection system, the system mayfurther include an indicator solvent reservoir containing an indicatorsolvent. In such implementations, the indicator chamber may include agranular or powder indicator and the plurality of valves may be furtherarranged such that fluid flow between the components is controllable topermit the indicator solvent in the indicator solvent reservoir to bedelivered to the indicator chamber in order to mix the indicator solventwith the granular or powder indicator to form the indicator. In somesuch implementations, the granular or powder indicator may include afunctionalized fluorophore. In some further such implementations, thefluorophore may be a rhodamine, and in some specific suchimplementations, the fluorophore may be rhodamine 123.

In some implementations of the THC detection system, the indicatorsolvent may be hydrochloric acid.

In some implementations of the THC detection system, the indicator maybe a diazo-functionalized reactant.

In some implementations of the THC detection system, the system mayfurther include a controller having one or more processors and a memory.The one or more processors may be communicatively connected with thememory and the memory may store computer-executable instructions forcontrolling the one or more processors to control the plurality ofvalves to facilitate: the conveying of the breath constituent samplefrom the elution port to the sample reservoir, the delivering of theindicator solvent to the indicator chamber to form the indicator, thecombining of the at least a first portion of the indicator with thebreath constituent sample to form the sample adduct, the combining ofthe at least a first portion of the solvent with the sample adduct, andthe delivering of the combined sample adduct and solvent to the opticalmeasurement chamber.

In some implementations of the THC detection system, the system mayfurther include a cleaning agent reservoir and the plurality of valvesmay be further arranged such that fluid flow between the components iscontrollable to permit a cleaning agent in the cleaning agent reservoirto be delivered to the optical measurement chamber. In some suchimplementations, the cleaning agent may be either ethanol oracetonitrile.

In some implementations of the THC detection system, the system mayfurther include a mixing chamber and the plurality of valves may befurther arranged such that fluid flow between the components iscontrollable to permit the sample adduct and the at least a firstportion of the solvent to be delivered to the mixing chamber and thenfrom the mixing chamber to the optical measurement chamber. In some suchimplementations of the system, the mixing chamber may include a shortsiphon and a long siphon that is longer than the short siphon, and theplurality of valves may be further arranged such that fluid flow betweenthe components is controllable to permit the sample adduct and the atleast a first portion of the solvent to be delivered to the mixingchamber via the long siphon and permit the combined sample adduct andsolvent to be removed from the mixing chamber via the short siphon fordelivery to the optical measurement chamber.

In some further such implementations of the system, the system may alsoinclude a controller having one or more processors and a memory. The oneor more processors may be communicatively connected with the memory andthe memory may store computer-executable instructions for controllingthe one or more processors to control the plurality of valves tofacilitate: the conveying of the breath constituent sample from theelution port to the sample reservoir, the combining of the at least afirst portion of the indicator with the breath constituent sample toform the sample adduct, the combining of at least the first portion ofthe solvent with the sample adduct, the delivering of the sample adductand the at least a first portion of the solvent to the mixing chamber,and the delivering of the combined sample adduct and solvent to theoptical measurement chamber.

In some implementations of the THC detection system, the system mayfurther include a pump and the plurality of valves may be furtherarranged such that fluid flow between the components is controllable topermit pressure from the pump to be applied to the mixing chamber so asto force the combined sample adduct and solvent into the short siphon.

The above implementations are only some of the implementations discussedherein, and do not constitute an exhaustive list of implementationsconsistent with the scope of this disclosure. Further implementationswill be evident from the more detailed discussion provided by theentirety of this disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

The various implementations disclosed herein are illustrated by way ofexample, and not by way of limitation, in the figures of theaccompanying drawings, in which like reference numerals refer to similarelements.

FIG. 1 depicts a schematic of an example target substance analysissystem.

FIG. 2 depicts the example target substance analysis system of FIG. 1during delivery of an eluent from a sample reservoir.

FIG. 3 depicts the example target substance analysis system of FIG. 1during recovery of an eluted breath constituent sample.

FIG. 4 depicts the example target substance analysis system of FIG. 1during delivery of an indicator solvent to an indicator chamber.

FIG. 5 depicts the example target substance analysis system of FIG. 1during recovery of a liquid indicator from the indicator chamber.

FIG. 6 depicts the example target substance analysis system of FIG. 1during delivery of a basic buffer to the eluted breath constituentsample.

FIG. 7 depicts the example target substance analysis system of FIG. 1during delivery of the indicator to the breath constituent sample.

FIG. 8 depicts the example target substance analysis system of FIG. 1during delivery of the indicator to a first calibration sample.

FIG. 9 depicts the example target substance analysis system of FIG. 1during delivery of the indicator to a second calibration sample.

FIG. 10 depicts the example target substance analysis system of FIG. 1during delivery of the combined indicator and first calibration sampleto a mixing chamber.

FIG. 11 depicts the example target substance analysis system of FIG. 1during delivery of a solvent to the mixing chamber.

FIG. 12 depicts the example target substance analysis system of FIG. 1during mixing of solvent and the combined indicator and firstcalibration sample.

FIG. 13 depicts the example target substance analysis system of FIG. 1during separation of the mixture in the mixing chamber.

FIG. 14 depicts the example target substance analysis system of FIG. 1during delivery of a separation layer to an optical measurement chamber.

FIG. 15 depicts the example target substance analysis system of FIG. 1during optical measurement of the contents of the optical measurementchamber.

FIG. 16 depicts the example target substance analysis system of FIG. 1during purging of the optical measurement chamber.

FIG. 17 depicts the example target substance analysis system of FIG. 1during purging of another portion of the analysis system.

FIG. 18 depicts the example target substance analysis system of FIG. 1during delivery of the combined indicator and sample to the mixingchamber.

FIG. 19 depicts the example target substance analysis system of FIG. 1during mixing of solvent and the combined indicator and sample.

FIG. 20 depicts the example target substance analysis system of FIG. 1during delivery of a separation layer from the mixing chamber to a firstactivation cell.

FIG. 21 depicts the example target substance analysis system of FIG. 1during delivery of the separation layer in the first activation cell tothe optical measurement chamber.

FIG. 22 depicts the example target substance analysis system of FIG. 1during delivery of the combined indicator and the second calibrationsample to the mixing chamber.

FIG. 23 depicts the example target substance analysis system of FIG. 1during mixing of solvent and the combined indicator and secondcalibration sample.

FIG. 24 depicts the example target substance analysis system of FIG. 1during delivery of a separation layer from the mixing chamber to asecond activation cell.

FIG. 25 depicts the example target substance analysis system of FIG. 1during delivery of the separation layer in the second activation cell tothe optical measurement chamber.

FIG. 26 depicts a variant of the target substance analysis system ofFIG. 1.

FIG. 27 depicts an isometric view of an example target substanceanalysis system.

FIG. 28 depicts a base station of the example target substance analysissystem without a cartridge or handheld breath collector moduleinstalled.

FIG. 29 depicts an isometric cutaway view of an example opticalmeasurement sensor.

FIG. 30 depicts an example cartridge.

FIG. 31 depicts the example cartridge of FIG. 30 with the cover removedto allow the internal components to be more clearly seen.

FIG. 32 depicts the same uncovered view of the example cartridge of FIG.30, but with various subassemblies exploded to allow for clearerviewing.

FIGS. 33 and 34 depict section views of an example mixing chamber.

FIG. 35 depicts a section view of an optical measurement chamber.

FIG. 36 depicts a section view of a first activation cell.

FIG. 37 depicts an example handheld breath collector module.

FIG. 38 is a photograph of a prototype cartridge during assembly; thisview gives some idea of the nature of the tubing connections between thecomponents.

FIG. 39 is a photograph of a prototype cartridge mounted into aprototype base station.

FIG. 40 is a photograph of another variant of a prototype cartridge witha layout similar to that in FIG. 26.

FIGS. 41 through 43 are color versions of FIGS. 38 through 40.

DETAILED DESCRIPTION

The analysis systems discussed herein generally employ aluminescence-based approach to measuring the amount of a targetsubstance, e.g., THC, in a person's breath. At a high level, a desiredquantity of a person's breath is flowed through some form of catchmedia, e.g., such as catch media in a small, portable, hand-held device,and then eluted; the resulting elution is then used as the “unknown”sample in the analysis system, and is subjected to one or more mixing,separation, and/or activation operations prior to being opticallyevaluated to determine an amount of THC that is present in the sample.

Quantitative detection of THC in human breath is challenging due to theextremely low concentration of THC in human breath and the presence ofmany common, similarly structured contaminants or chemicalinterferences. As disclosed herein, breath constituents from one or more(e.g., 1-3) exhalations may be captured with a handheld device forroadside analysis. Any THC in a breath sample taken with the device canbe captured by adsorption on a catch medium or catch media. THC adsorbedon the catch medium may be eluted from the capture medium using a polarorganic solvent. A basic buffer and an aqueous diazotized fluorophoresolution may then be added to the capture solution to form afluorescent-labeled THC adduct in a sample adduct solution having abasic pH.

After formation of the adduct solution, a nonpolar organic solvent maybe added to the sample adduct solution, the resulting mixture vigorouslymixed, and the mixture then allowed to separate into polar and nonpolarphase layers. Any fluorescent-labeled THC-adduct will be contained inthe nonpolar layer, and thereby isolated by solvent extraction frommolecular species that dissolved in polar, but not nonpolar solvents.

Once the sample adduct, if any, is isolated in the nonpolar fraction ofthe solvent extraction, it can then be detected and quantified byoptical techniques, for example measuring the fluorescence of thefluorescent-labeled adduct and determining a quantity of any THCcaptured from the original breath sample based on the measuredfluorescence.

FIG. 1 depicts a schematic of an example target substance analysissystem. In FIG. 1, the example target substance analysis system isconfigured to facilitate the detection of tetrahydrocannabinol (THC) ina person's breath, thereby allowing for “Breathalyzer®” type testing forpeople suspected of being under the influence of THC. As will beappreciated from the following discussion, the detection of THC in abreath sample may involve a number of different steps, and it is to beunderstood that while these steps are described with respect to aparticular embodiment of a THC analysis system, other embodimentsfalling within the scope of this disclosure may operate differently fromthe specific examples discussed but may nonetheless still fall withinthe scope of the disclosure.

In FIG. 1, the analysis system 100 includes components grouped intothree general assemblies: a cartridge 102, a base station 104, and abreath capture module 106. These three assemblies may be interconnectedor disconnected during operation to facilitate the analysis of acaptured breath constituent sample. It is to be understood that otherimplementations of the concepts discussed herein may offer similarcapabilities, but without one or more of such assemblies (or usingsimilar, but different, assemblies).

In the depicted implementation, components relating to the collection ofa breath constituent sample from a subject may be contained in a breathcapture module (BCM) 106. Such a BCM may be designed to be relativelylightweight and may have features, such as a catch media 114, that areconfigured to promote the capture of breath constituents from a person'sbreath as the person exhales through the BCM 106. The BCM 106 may, forexample, be a BCM such as those described in U.S. Patent Application No.62/337,286, previously incorporated by reference herein. In someimplementations, the BCM 106 may include a plurality of microbeads ormicrospheres, as discussed in U.S. Patent Application No. 62/337,286,that are sandwiched between and retained by two mesh screens. In somesuch implementations, a woven or fibrous filter media or membrane may beinterposed between each mesh screen and the microbeads or microspheres;such a woven or fibrous filter media or membrane may provide furthersurface area onto which breath constituents may adsorb during samplecollection and may enhance the ability of the BCM 106 to capture usefulsamples. For example, in some implementations, the BCM 106 may includeone or more layers of filter media such as Technostat® 90 Plus, which isa meltblown synthetic fiber carried on a spunbond polypropylene backingmaterial. Technostat® 90 Plus is manufactured by Hollingsworth & Vose ofEast Walpole, Mass., and is distributed in the United States of Americaby Superior Felt & Filtration of McHenry, Ill., at the time of thiswriting. In implementations utilizing Technostat® 90 Plus or a similarfilter media, the BCM 106 may, in some instances, omit additional filtermedia such as microbeads and instead rely on one or more layers of thefilter media. In some such implementations, the filter media may besandwiched between mesh screens to provide support to the filter mediaand to prevent the filter media from getting dislodged. In other suchimplementations, the filter media may not be sandwiched between meshscreens but may be clamped in place directly, e.g., about the peripheryof the filter media.

The BCM 106 may also include a mouthpiece 108, to allow the person toexhale into the BCM 106, and a saliva trap 110, which may prevent orhinder saliva or spittle from reaching the catch media 114. The BCM mayalso include electronics (not shown), such as one or more processors anda memory storing instructions for controlling the one or moreprocessors, that may control or monitor operation of the BCM 106 andprovide information regarding the progress of the sample collectionusing the BCM 106. For example, the BCM 106 may include a pressuresensor 112 that has a pressure measurement port that is interposedbetween the saliva trap 110 and the catch media 114 so as to monitor thepressure downstream of the saliva trap 110 and upstream of the catchmedia 114. The one or more processors may monitor the data from thepressure sensor and determine therefrom the amount of air that is blowninto the mouthpiece 108, through the saliva trap 110, and then deliveredto the catch media 114. When the amount of exhaled breath that passesthrough the BCM 106 exceeds a predetermined amount (as determined fromthe pressure sensor data, or from another sensor providing similarinformation), e.g., 3 liters, then the one or more processors may causea signal to be provided that a sufficient sample has been collected,e.g., the BCM 106 may be caused to emit a “beep” or provide some othersort of indication that a sufficient sample has been collected.

After a breath constituent sample is collected in the BCM 106, the BCM106 may be connected to the cartridge 102 to allow the breathconstituent sample to be drawn out of the BCM 106 and analyzed by theanalysis system 100.

The cartridge 102 may include a number of reservoirs that containvarious chemicals used in the target substance detection techniques usedby the analysis system 100. These reservoirs may be configured to allowthe fluids contained in each reservoir to be independently dispensed, asneeded, during the analysis process. In some cases, one or more thereservoirs may also be configured to allow fluids outside of thereservoirs to be drawn into the reservoir. In the depicted exampleanalysis system 100, the reservoirs 120 take the form of syringes, eachof which is actuated by a corresponding actuator 118. The actuators 118may be located in the base station 104, which may be a larger unit thatincludes various “durable” systems or components, e.g., the actuators118, an optical sensor 152, electronics (not shown), power supplycomponents (not shown), etc. The cartridge, which may include various“consumable” elements, e.g., chemicals used during the analysis, may beremovably insertable or connectable with the base station to allow foreasy replacement of the consumable elements.

It is to be understood that while syringes and actuators are used in thedepicted example system, other fluid storage and dispensing systems maybe used in place of, or in addition to, such syringe-based systems. Suchalternative implementations are to be understood as also being withinthe scope of this disclosure.

In the depicted example, each of the reservoirs 120 is connected to acommon manifold 128 (which may, for example, be provided by two or moreseparate manifolds 130 and 132 that are linked together via a tube orother connection so as to form the common manifold 128; this was done toallow commercial off-the-shelf manifolds to be used, and could beavoided by custom-manufacturing a single, integrated manifold). Eachsuch connection of a reservoir 120 to the manifold 128 may include acorresponding valve 122 that may be opened or closed to prevent fluidflow between the corresponding reservoir 120 and the manifold 128. Insome instances, there may be an additional diverter or 3-way valve thatis also interposed between some of the reservoirs 120 and the manifold128 to allow the fluid that is stored in such reservoirs to be deliverednot only to the manifold 128, but also alternatively to anotherlocation. In such scenarios, the functionality of the diverter valve andthe shut-off valve may be combined into a single valve structure, e.g.,a 3-way valve with an integral shut-off capability.

The common manifold may also be configured to allow fluids from thereservoirs 120 to be directed to one or more downstream components, suchas a mixing chamber 136, a first activation cell 142, a secondactivation cell 144, an optical measurement chamber 146, a wastereceptacle 148, or other downstream components.

FIGS. 2 through 25 depict the example analysis system of FIG. 1 duringvarious operational phases, and will be referred to in the followingdiscussion describing the operation of the example analysis systemduring a typical breath constituent analysis. For clarity, certainconventions are adopted in these Figures. For example, valves arerepresented by two or three triangles pointing towards a common centerpoint; each triangle may represent a port on the valve—if a triangle isblack, this indicates that fluid may flow through the port correspondingto that triangle; if a triangle is white, this indicates that fluid isprevented from flowing through the port corresponding to that triangle.Additionally, white arrows have been overlaid on flow paths to indicatethe direction of fluid flow at that point in the analysis process.

In FIG. 2, the analysis may begin with the collection of the breathconstituent sample from the BCM 106. To begin with, the BCM 106 may beconnected to an elution port in the cartridge 102 (or a similar port onthe base station 104), and an eluent may be delivered from a samplereservoir 120 a to the elution port and thereby to the catch media 114of the BCM 106. For example, a three-way valve 124 a may be actuatedsuch that the sample reservoir 120 a is in fluidic communication withthe catch media 114. A sample actuator 118 a may then be actuated so asto meter out a desired amount of eluent from the sample reservoir 120 aand deliver the metered out amount of eluent to the catch media 114. Forexample, 250 μL of eluent may be dispensed from the sample reservoir 120a and delivered to the catch media 114.

The eluent, which may, for example, be ethanol (EtOH), may then beallowed soak the catch media 114, e.g., for approximately 30 seconds, soas to elute any breath constituents that have adsorbed onto the catchmedia 114 into the eluent. After the catch media 114 has been soaked bythe eluent for a sufficiently long enough period of time to result inmost of the breath constituents being eluted, the resulting eluent andeluted breath constituents may be withdrawn from the BCM 106 andreturned to the sample reservoir 120 a, as shown in FIG. 3. For example,this may be achieved by causing the sample actuator 118 a to be operatedin the reverse manner as it was while delivering the eluent from thesample reservoir 120 a to the catch media 114, e.g., as in FIG. 2. It isto be understood that, if desired, the eluent may be returned to anotherreservoir (not pictured) which may be sterile or otherwiseuncontaminated after collection—as such a solution would involve furthercomponents and complexity for little or no benefit, the implementationdescribed herein returns the eluent and eluted breath constituents tothe sample reservoir 120 a to await further processing.

After the elution and collection of the breath constituent sample, thesystem may be operated so as to add an aqueous diazotized fluorophoresolution to the eluted breath constituent sample to produce an adductwith THC molecules that may be in the breath constituent sample. In thepresent example analysis system, such an aqueous diazotized fluorophoresolution may be generated by mixing an indicator solvent with asolid-phase indicator to create the aqueous diazotized fluorophoresolution, although it is envisioned that such mixing may be unnecessaryif alternative aqueous diazotized fluorophore solutions are used thatare stable when in liquid form.

The aqueous diazotized fluorophore solution may be produced just before,during, or just after the elution of the breath constituent sample fromthe catch media 114. For example, a three-way valve 124 b may beactuated so as to put an indicator solvent reservoir 120 b containing anindicator solvent in fluidic communication with an indicator chamber 126containing a solid-phase indicator. The indicator solvent reservoir 120b containing the indicator solvent may be actuated by an indicatorsolvent actuator 118 b so as to dispense a quantity of the indicatorsolvent into the indicator chamber 126 that contains the solid-phaseindicator, as shown in FIG. 4. After the indicator solvent has beenintroduced into the indicator chamber 126, the solid-phase indicator maybe allowed to dissolve into the indicator solvent for a long enoughinterval to produce a desired quantity of liquid-phase indicator.

The indicator solvent may be acidic, e.g., 100 μM hydrochloric acid(HCl), and may be added in sufficient quantity so as to produce enoughindicator so as to be able to provide equal doses of indicator to thesample reservoir 120 a and to one or more calibration sample reservoirs(if used). In the example analysis system of FIG. 1, at least 750 μL ofindicator solvent may be added to the solid-phase indicator in theindicator chamber 126 to allow for the later delivery of 250 μL ofliquid indicator to each of the three sample reservoirs. Aftersufficient dissolution time has elapsed, the liquid-phase indicator thatis present in the indicator chamber 126 may be returned to the indicatorsolvent reservoir 120 b, e.g., by actuating the indicator solventactuator 118 b in a reverse manner from how it was actuated in order todeliver the indicator solvent to the indicator chamber 126, as shown inFIG. 5. In some implementations, the indicator solvent actuator 118 bmay be repeatedly actuated so as to drive the mixture of indicatorsolvent and solid-phase (or dissolving) indicator into and out of theindicator solvent reservoir 120 b so as to promote better mixing anddissolution between the indicator solvent and the solid-phase indicator.

Once the indicator has been formed and the breath constituent samplecollected, the indicator may then be combined with the eluted breathconstituent sample, as well as with any calibration samples that may beused in the analysis system, to form a fluorescent-labeled THC adductthat may later be used to determine the amount of THC present in eachsample. In the example analysis system, two calibration samples areprovided, although similar analysis systems may utilize more or less (orno) calibration samples, depending on the accuracy desired or whetheralternative calibration mechanisms are used. In the present exampleanalysis system, a negative calibration sample and a positivecalibration sample are both used. The negative calibration sample has noTHC present but includes a similar type and quantity of fluid as wasused to elute the breath constituent sample, and may be stored, forexample, in a first calibration sample reservoir 120 c. Conversely, thepositive calibration sample has a known amount of THC present in asimilar type and quantity of fluid as was used to elute the breathconstituent sample, and may be stored, for example, in a secondcalibration sample reservoir 120 e. The positive calibration sample mayhave an amount of THC thought to be slightly higher, e.g., 10% higher,than the amount of THC that could reasonably be expected to be in aneluted breath constituent sample so that the fluorescent response of thebreath constituent sample during the analysis is bracketed by thepositive and negative calibration samples. However, it is to beunderstood that other implementations may, for example, include anon-zero negative control (not truly negative) or a positive controlthat is lower than the expected maximum quantity of THC that couldreasonably be expected to be in the eluted breath constituent sample.For example, if the legal framework surrounding marijuana evolves toallow some amount of THC to be present in a person's breath before theperson is considered to be “impaired,” then the negative control may bepegged to this lower limit instead of zero.

Fluorescent-labeled THC adducts are stable when in a basic solution, butmay rapidly degrade when exposed to an acidic environment. Conversely,the aqueous diazotized fluorophore solution may be stable in an acidicsolution, e.g., such as when dissolved in hydrochloric acid. In order toincrease the longevity of the THC adducts that may result from mixing ofthe liquid-phase indicator with the eluted breath constituent sampleand/or the calibration samples, the eluted breath constituent sample andthe calibration samples may be combined with a basic buffer that mayprevent or mitigate the degradation of any THC adducts that are formedwhen the eluted breath constituent sample and/or the calibration samplesare combined with the liquid-phase indicator, e.g., by raising the pH ofthe eluted breath constituent sample and/or the calibration samplessufficiently high enough that the subsequent addition of an acidicindicator solution to the eluted breath constituent sample and/or thecalibration samples does not cause the THC adduct to degradesignificantly (or at all).

In the case of the sample reservoir 120 a, the buffer may be added afterthe elution process has completed and the eluted breath constituentsample has been retrieved from the BCM 106. This prevents the bufferfrom diluting the eluent, which may potentially reduce its effectivenessin eluting the breath constituents. The amount of buffer used may, insome implementations, be significantly larger than the amount of eluent,e.g., 500 μL of buffer may be added to 250 μL of eluent, so the buffermay be the dominant mixture component after combination. In order toprevent the buffer from potentially hindering the elution of the breathconstituents from the BCM 106, the buffer may be added to the samplereservoir 120 a after the breath constituents have already been eluted.For example, a buffer valve 122 d and a sample valve 122 a may beopened, and the 3-way valve 124 a may be actuated to as to place thesample reservoir 120 a into fluidic communication with the manifold 128.The buffer may then be delivered to the sample reservoir 120 a byactuating a buffer actuator 118 d that drives the buffer out of a bufferreservoir 120 d.

In the case of the calibration sample reservoirs, the buffer may beintroduced in a similar manner or may, as is the case in thisimplementation, be pre-loaded into the calibration sample reservoirsduring cartridge assembly or preparation.

After the eluted breath constituent sample and/or the calibrationsamples have been provided with the buffer from the buffer reservoir 120d, the indicator solution from the indicator reservoir 120 b may bedispensed to the sample reservoir 120 a, the first calibration samplereservoir 120 c, and the second calibration sample reservoir 120 e. Thedistribution of the indicator to the sample reservoir 120 a, the firstcalibration sample reservoir 120 c, and the second calibration samplereservoir 120 e may be performed simultaneously or sequentially, e.g.,in sequence with each distribution of indicator occurring immediatelyafter (or otherwise very close in time after) the previous distributionof indicator. For example, in FIG. 7, the 3-way valves 124 a and 124 band the buffer valve 122 a and an indicator solvent valve 122 b havebeen actuated so as to put the sample reservoir 120 a and the indicatorsolvent reservoir (now containing the liquid indicator solution) 120 b,respectively, in fluidic communication with the manifold 128, thusallowing liquid-phase indicator to be pushed out of the indicatorsolvent reservoir 120 b by the actuator 118 b and into the samplereservoir 120 a. Similarly, the indicator solvent valve 122 b and thefirst calibration sample valve 122 c may both be opened (and the othervalves 122 on the manifold 128 closed) to put the indicator solventreservoir 120 b in fluidic communication with the first calibrationsample reservoir 120 c via the manifold 128, as shown in FIG. 8. Asimilar quantity of liquid indicator may then be delivered to the firstcalibration sample reservoir 120 c by actuating the indicator solventactuator 118 b. The second calibration sample reservoir 120 e may alsobe provided with liquid indicator in a similar manner, e.g., by openingthe indicator solvent valve 122 b and a second calibration sample valve122 e (and closing the other valves on the manifold 128), as shown inFIG. 9, and driving the liquid indicator from the indicator solventreservoir into the second calibration sample reservoir 120 e using thesolvent indicator actuator 118 b.

Once the liquid indicator has been added to the eluted sample in thesample reservoir 120 a, as well as the first calibration samplereservoir 120 c and the second calibration sample reservoir 120 e, ifused, the amount of THC adduct (if any) that is present in each of thesamples may be evaluated. In the example implementation, this occurs ina serial fashion using a largely common set of components locateddownstream of the manifold 128; these components are washed in betweenanalysis runs in order to prevent cross-contamination of the samples. Inother implementations, separate, parallel downstream systems may be usedinstead, thereby preventing cross-contamination.

During operation of the example analysis system, the first calibrationsample valve 122 c and a manifold valve 122 h may both be placed in openstates to put the first calibration sample reservoir in fluidiccommunication with the manifold 128 and, via the manifold 128, a mixingchamber 136. This assumes that the first calibration sample is used; inimplementations where such a calibration sample is not used, thisportion of the process may be omitted. The first calibration sample,which is a negative calibration sample having no adduct in this case(since there is no THC in it), may then be delivered from the firstcalibration sample reservoir 120 c to the mixing chamber 136 byactuating the first calibration sample actuator 118 c, e.g., such as isshown in FIG. 10. Subsequent to the introduction of the firstcalibration sample to the mixing chamber, the first calibration samplevalve 122 c may be closed and a solvent valve 122 f may be opened to puta solvent reservoir 120 f into fluidic communication with the mixingchamber 136 via the manifold 128. A solvent actuator 118 f may beactuated to cause the solvent reservoir 120 f to dispense a solventwithin the solvent reservoir 120 f into the mixing chamber 136 via themanifold 128, as is shown in FIG. 11. The solvent, for example, may be amixture of methyl tertiary butyl ether (MTBE) and heptane or a similarsolvent. In some implementations, the delivery of the solvent and thesample (be it a calibration sample or the breath constituent sample) tothe mixing chamber 136 may be done in alternating, piecemeal fashion soas to preliminarily mix the two fluids more effectively.

The mixing chamber 136 may serve a two-fold purpose—it may act as atemporary holding area or reservoir for the current sample in whichmixing with the solvent may occur and it may also be used as a vessel inwhich polar/non-polar phase separation may be used in order to separateout a non-polar layer containing the THC adduct from a polar layer ofthe mixture. The mixing chamber may have multiple inlets into thechamber, e.g., a long siphon 140, a short siphon 138, and, in somecases, a pressurization inlet (not labeled, but connected to 3-way valve124 c). The long siphon 140 may extend to the bottom of the mixingchamber 136 such that the mixing chamber 136 may be completely drainedby drawing whatever fluids are within the mixing chamber 136 out throughthe long siphon 140. The short siphon 138, however, may only extendpartway down the mixing chamber 136—the length of the short siphon 138may be designed such that the short siphon 138 extends nearly to thebottom (but not past the bottom) of the separation layer containing theTHC adduct after separation has occurred. This allows the short siphon138 to be used to siphon off the THC adduct after separation for furtherprocessing.

After the combined first calibration sample and liquid indicator and thesolvent are both delivered to the mixing chamber 136, the deliveredmixture may be withdrawn and re-introduced into the mixing chamber 136multiple times, e.g., by reciprocating the first calibration sampleactuator 118 c multiple times, thereby drawing the mixture back into thefirst calibration sample reservoir 120 c and then re-delivering it tothe mixing chamber 136 repeatedly, e.g., such as is shown in FIG. 12,which may agitate the mixture and further promote thorough and completemixing of the solvent with the sample. After such mixing, the mixedsolution may be allowed to rest within the mixing chamber 136 so thatthe mixed solution may separate out into polar and non-polar phases,e.g., such as is shown in FIG. 13.

Once the adduct/solvent/indicator solution has separated in the mixingchamber 136, the separated THC adduct may be delivered to the opticalmeasurement chamber 146, as shown in FIG. 14. For example, 3-way valves124 d, 124 e, and 124 f may all be set so as to put the mixing chamber136 in fluidic communication with the optical measurement chamber 146.Another 3-way valve 124 c may be actuated so as to put an air pump 154in fluidic communication with the mixing chamber 136; when the air pump154 is actuated, the resulting pressure increase in the mixing chamber136 may drive the separated THC adduct into the short siphon 138 andthen into the optical measurement chamber 146.

After the first calibration sample is delivered to the opticalmeasurement chamber 146, the first calibration sample may be opticallymeasured to determine an amount of THC adduct, and thus an amount ofTHC, that is present in the first calibration sample, e.g., such as isshown in FIG. 15. Such optical measurement may be made by opticallystimulating the adduct using light having a first set of wavelengths andthen measuring the amount of light having a second set of wavelengthsthat is then emitted by the THC adduct in the sample in response to suchoptical stimulation.

Such optical measurement readings may involve a multi-step process. Tobegin with, the temperature of the optical sensor 152 may be measuredfor a brief period of time, e.g., 100 ms, and then an opticalmeasurement may be obtained without any illumination of the sample inthe optical measurement chamber 146, e.g., for a 100 ms period. Thetemperature reading may be used to assist in calibrating the output ofthe optical sensor 152, if necessary (for example, photosensor outputvoltage may depend on both photosensor temperature and the amount oflight that is detected). Subsequent to such a “dark” reading, a “light”reading may be obtained, e.g., one in which the sample is illuminated bythe optical source that is used. Again, this may be for a period oftime, e.g., 100 ms. The “dark” reading, e.g., the average “dark”reading, may be subtracted from the “light” reading, e.g., the average“light” reading, in order to compensate for any noise-related effectsthat may affect the results.

In this example, the first calibration sample is a true negative sample,i.e., there is no THC present (and thus no adduct will be formed). Thus,the optical measurement will generally result in a reading of zero,although there may be some low-level luminescence at the frequencies ofinterest due, for example, to potential contaminants or other sources oflight in the sample solution. If present, these low-level luminescencereadings may serve as a baseline of what a “zero” reading shouldcorrespond to.

After the optical measurement has been obtained, the measured firstcalibration sample may be delivered from the optical measurement chamber146 to a waste reservoir 148, as shown in FIG. 16. In this particularimplementation, such a purge operation may be performed by adjusting3-way valves 124 c, 124 d, and 124 e such that the air pump 154 is influidic communication with the optical measurement chamber 146. Oncesuch a fluidic connection has been made, the air pump 154 may beactuated so as to apply positive pressure to the optical measurementchamber 146, thereby driving the first calibration sample out of theoptical measurement chamber 146 and into the waste reservoir 148. Afterthe optical measurement chamber 146 has been purged, the mixing chamber136 and the manifold 128 may be purged in a similar manner, such as isshown in FIG. 17. In this case, the three-way valve 124 d may beactuated so as to divert air flow from the air pump 154 to the mixingchamber 136 via the short siphon 138, and the manifold valve 122 h and amanifold waste valve 122 i may be actuated so as to place the mixingchamber 136 in fluidic communication with the waste reservoir 148. Theresulting air pressure may force the fluids in the mixing chamber 136into the long siphon 140, thereby driving such fluids back through themanifold 128 and into the waste reservoir 148; a vent 150 may allow theair that is used for such purposes to escape while keeping the usedsample in the waste reservoir 148.

After the first calibration sample solution has been purged from theoptical measurement chamber 146, the manifold 128, the mixing chamber136, the optical measurement chamber 146, and any other components thatcame into contact with the first calibration sample may be washed with acleaning agent delivered from a cleaning agent reservoir 120 g. Suchcleaning may be accomplished by opening a cleaning agent valve 122 g andthen driving a cleaning agent out of the cleaning agent reservoir 120 gusing a cleaning agent actuator 118 g. The various valves in theanalysis system 100 may be actuated so as to route the cleaning agentthrough the various components with which the first calibration samplecame into contact and then ultimately to the waste reservoir. Suchrouting may be similar to the manner in which the air from the air pump154 was routed through the analysis system 100, e.g., such as depictedin FIGS. 16 and 17. After the cleaning agent is routed through theanalysis system 100, the cleaned components of the analysis system 100may be dried by flowing air from the air pump 154 along the same flowpaths.

This same process, e.g., the steps depicted in FIGS. 10 through 17 (andthe purge and cleaning steps), may be repeated, with some slightdifferences, for the eluted breath constituent sample and well as forthe second calibration sample. Such further processing is discussedbelow.

After the optical measurement chamber 146 and the mixing chamber 136 arecleaned, the combined eluted breath constituent sample and liquidindicator may be delivered to the mixing chamber 136 from the samplereservoir 120 a, e.g., by opening the sample valve 122 a and themanifold valve 122 h and actuating the sample actuator 118 a (with the3-way valve 124 a actuated so as to place the sample reservoir 120 a andthe manifold 128 into fluidic communication. Thus, the combined elutedbreath constituent sample and liquid indicator may be delivered to themixing chamber 136, as shown in FIG. 18.

Once the combined eluted breath constituent sample and liquid indicatorhave been delivered to the mixing chamber 136, the solvent from thesolvent reservoir 120 f may be delivered to the mixing chamber,essentially repeating the process depicted in FIG. 11. Once the solventhas been delivered to the mixing chamber 136, the solvent and thecombined eluted breath constituent sample and liquid indicator may bemixed by reciprocating the sample actuator 118 a to repeatedly draw thefluid in the mixing chamber 136 in and out of the sample reservoir 120 aas shown in FIG. 19, similar to how the first calibration sample wasmixed in FIG. 12.

Once the mixing of the solvent and the combined eluted breathconstituent sample and liquid indicator has been completed, the mixturemay be allowed to separate, similar to the separation depicted in FIG.13. Once the mixture has separated, the sample THC adduct may besiphoned off through the short siphon 138, e.g., by pressurizing themixing chamber using the air pump 154. The valves 124 d and 124 e may beactuated such that the sample THC adduct is conveyed to the firstactivation cell 142, as shown in FIG. 20. The first activation cell 142may be configured to activate the sample THC adduct, i.e., cause the THCadduct to transition to a state in which it is photo-reactive so that itwill luminesce when stimulated with a particular wavelength orwavelengths of light. In some implementations, the first activation cell142 may be coated with a hydrophobic coating or other coating thatinteracts with the sample THC adduct in order to activate it. In someimplementations, the first activation cell may be a pipette tip producedusing StarLab International GmbH's Repel Polymer Technology (RPT),(examples of such pipette tips are, for example, the “TipOne® RPT” soldby USA Scientific, and, more specifically, the 1000 μL XL TipOne® RPT,part number 1182-1830), which may be used to produce an optimizedconventional polypropylene surface that is extremely hydrophobic; suchpipettes have been tested and have proven to be effective at activatingTHC adducts such as rhodamine-123, as compared with other types ofpipette tips that are not able to activate rhodamine-123. In someimplementations, there may be one activation cell for each sample thathas or may have THC in it, as the process of activating the THC adductin a given sample may consume the coating or other catalyst that causesthe activation.

After the sample THC adduct has been activated in the first activationcell 142, the 3-way valve 124 c may be actuated to put the air pump 154in fluidic communication with the first activation cell 142 via apneumatic manifold 134, and the 3-way valves 124 e and 124 d may beactuated so as to put the first activation cell 142 into fluidiccommunication with the optical measurement chamber 146. The sample THCadduct may then be driven out of the first activation cell 142 by airfrom the air pump 154, as shown in FIG. 21, and into the opticalmeasurement cell 146. Once the sample THC adduct is in the opticalmeasurement cell 146, a measurement of the amount of THC adduct that iswithin the optical measurement cell 146 may be obtained in the samemanner as described above with respect to FIG. 15, and then the analysissystem 100 may be purged and cleaned, as discussed above with respect toFIGS. 16 and 17, and cleaned and dried, as also discussed above.

After the sample THC adduct has been measured and routed to the wastereservoir 148, the second calibration sample may be analyzed. Suchanalysis may begin with the delivery of the second calibration sample tothe mixing chamber 136. For example, a second calibration sample valve122 e may be opened and the second calibration sample actuator 118 e maybe actuated to drive the combined second calibration sample and liquidindicator into the mixing chamber via the long siphon 140.

Once the combined second calibration sample and liquid indicator havebeen delivered to the mixing chamber 136, the solvent from the solventreservoir 120 f may be delivered to the mixing chamber as shown in FIG.22, essentially repeating the process depicted in FIG. 11. Once thesolvent has been delivered to the mixing chamber 136, the solvent andthe combined second calibration sample and liquid indicator may bemixed, as shown in FIG. 23 by reciprocating the second calibrationsample actuator 118 e to repeatedly draw the fluid in the mixing chamber136 in and out of the second calibration sample reservoir 120 a, similarto how the first calibration sample was mixed in FIG. 12.

Once the mixing of the solvent and the combined second calibrationsample and liquid indicator has been completed, the mixture may beallowed to separate, similar to the separation depicted in FIG. 13. Oncethe mixture has separated, the second calibration sample THC adduct maybe siphoned off through the short siphon 138, e.g., by pressurizing themixing chamber 136 using the air pump 154. The valves 124 d, 124 e, and124 f may be actuated such that the second calibration sample THC adductis conveyed to the second activation cell 144, as shown in FIG. 24. Thesecond activation cell 144 may be similar to the first activation cell142 and serve a similar purpose, but with respect to the secondcalibration sample adduct, i.e., it may be used to activate the secondcalibration sample adduct.

After the second calibration sample THC adduct has been activated in thesecond activation cell 144, the 3-way valve 124 c may be actuated to putthe air pump 154 in fluidic communication with the first activation cell142 via a pneumatic manifold 134, and the 3-way valves 124 f, 124 e, and124 d may be actuated so as to put the second activation cell 144 intofluidic communication with the optical measurement chamber 146. Thesecond calibration sample THC adduct may then be driven out of thesecond activation cell 144 by air from the air pump 154, as shown inFIG. 25, and into the optical measurement cell 146. Once the secondcalibration sample THC adduct is in the optical measurement cell 146, ameasurement of the amount of THC adduct that is within the opticalmeasurement cell 146 may be obtained in the same manner as describedabove with respect to FIG. 15, and then the analysis system 100 may bepurged and cleaned, as discussed above with respect to FIGS. 16 and 17,and cleaned and dried, as also discussed above.

FIG. 26 depicts a variant of the target substance analysis system ofFIG. 1. In FIG. 26, a pressure relief valve 178 has been added to thepneumatic manifold 134 to allow pressure that may build up in theactivation cells 142 or 144 to be relieved. Such a pressure valve may,for example, activate to release excess pressure when the pressure inthe pneumatic manifold 134 exceeds 3 psi above ambient levels.

FIGS. 27 through 37 show various example views of an analysis system, orcomponents thereof, that may be used in the manner described above withrespect to FIGS. 1 through 24. For ease of reference, the components inFIGS. 27 through 37 that correspond to components in FIGS. 1 through 24are identified by reference numbers having the same last two digits asthe corresponding components or element in FIGS. 1 through 24.

FIG. 27 depicts an isometric view of an example target substanceanalysis system. The analysis system 200 may include, for example, threeseparate modules—a base station 204, a cartridge 202, and a handheldbreath capture module (BCM) 206. The analysis system may have anexterior housing (not shown) that covers and protects the internalcomponents during use.

FIG. 28 depicts the base station 204 without the cartridge 202 or thehandheld BCM 206 installed. As can be seen, the base station may includemultiple actuators, such as actuators 218 a through 218 g, which may beused to control how fluids are dispensed from or drawn into thereservoirs that are included in the cartridge 202. In the cartridge 202,the reservoirs that are included are provided in the form of syringes;when the cartridge 202 is installed in the base station 204, eachactuator 218 may interface with a plunger of a corresponding syringe andmay be actuated so as to move the plunger into or out of the syringe,thus causing fluids to be driven from or sucked into thesyringe/reservoir.

The base station may also include an optical measurement sensor 252 thatmay be configured to obtain luminescence readings from samples that areprocessed in the cartridge 202. The optical measurement sensor 252, inthis implementations, projects an optical beam 264 having a firstwavelength range that is selected so as to stimulate emission of lighthaving a second wavelength range from the THC adduct. The emitted lightmay then be collected by the same optics used for projection and routedto a photodetector in the optical measurement sensor 252 forquantification. FIG. 29 depicts an isometric cutaway view of an exampleoptical measurement sensor 252. A photoemitter 266 may be located so asto direct light along a first axis (the vertical axis with respect tothe orientation of FIG. 29), and a photodetector 268 may be configuredto receive light received along a second axis that is orthogonal to thefirst axis. A beam splitter 270, e.g., a window that is generallyreflective to the first wavelength range but generally transmissive tothe second wavelength range, may be located at the intersection of thefirst axis and the second axis, and may be positioned at a 45° angle toboth axes so as to cause light from the photoemitter 266 to be turned90° and directed out of the optical measurement sensor 252 to form theoptical beam 264. At the same time, light that is emitted by the THCadduct in response to stimulation by the light of the first wavelengthrange may pass through the beam splitter 270 without being reflected andthus be received by the photodetector 268. When measurement of theamount of THC adduct present in a sample is desired, the photoemitter266 may be turned on so that light of the first wavelength range isemitted to optically pump or stimulate the THC adduct; the light of thesecond wavelength range that is emitted by the THC adduct in responsemay then be measured by the photodetector 268, and the intensity of suchdetected light may be correlated with an amount or concentration of THCadduct (and thus THC) that is present in the sample.

It is to be understood that other types of optical sensors may be usedas well, and that some optical sensors may, depending on the particularadduct used, not include a photoemitter, e.g., in implementations wherethe THC adduct does not require optical pumping in order to emit light.

FIG. 30 depicts an example cartridge 202; the cartridge may have aprotective cover (as depicted) and house within it most or all of the“wet” chemistry components that are used in the analysis process. Inaddition to reservoirs 220 a through 220 g, the cartridge 202 may alsoinclude an elution port 256 that may connect with a catch media of thehandheld BCM 206. The cartridge 202 may also have mechanical featuresand electrical connections for interfacing the cartridge 202 with thebase station 204 and with the handheld BCM 206.

FIG. 31 depicts the example cartridge 202 with the cover removed toallow the internal components to be more clearly seen. FIG. 32 depictsthe same uncovered view of the example cartridge 202, but with varioussubassemblies exploded to allow for clearer viewing. It is to beunderstood that the components depicted and described below may beconnected together by flexible tubing that provides fluidic connectionsbetween the various ports of the components depicted. Such tubing is notdepicted in these Figures since the number of tubes and the routing ofthe tubes would clutter the Figures and impact their clarity. However,it is to be understood that the components depicted in FIGS. 31 and 32are, in actual practice, connected by such tubing, and that such tubingrouting/connections may be consistent with the fluidic connections androuting shown in FIG. 1.

In FIGS. 31 and 32, it may be seen that reservoirs 220 are arranged in arow and supported by a common interface block that positions eachreservoir 220 in a particular position that allows each 220 to interfacewith a corresponding one of the actuators 218 when the cartridge 202 isinstalled in the base station 204. A sample reservoir 2020 a, a solventreservoir 2020 f, a buffer reservoir 2020 d, a second calibration samplereservoir 2020 e, an indicator solvent reservoir 2020 b, a firstcalibration sample reservoir 2020 c, and a cleaning agent reservoir 2020g are depicted. It is to be understood that the order and relativepositioning of these reservoirs may be different in variousimplementations, and that the particular placement of such reservoirsmay be selected taking into account various considerations, such asminimization of tubing lengths (to reduce dead volumes), standardizationof tubing lengths (to facilitate assembly), etc.

Also visible in FIGS. 31 and 32 are features for interfacing with thehandheld BCM 206, e.g., the elution port 256, as well as an electricalinterconnect 258 that may allow the cartridge 202 or the base station204, via the cartridge 202, to communicate with the electronics of thehandheld BCM 206.

In the implementation depicted in FIGS. 31 and 32, the valves 222 areintegrated into the manifolds 230 and 232 (rather than being separate,as suggested in FIG. 1) to reduce the potential dead volume in themanifold that is formed by the two manifolds 230 and 232. Thus, themanifold 230 may include a buffer valve 222 d, a sample valve 222 a, anindicator solvent valve 222 b, a first calibration sample valve 222 c,and a manifold valve 222 h. Correspondingly, the manifold 232 mayinclude a second calibration sample valve 222 e, a solvent valve 222 f,a cleaning agent valve 222 g, and a manifold waste valve 222 i. 3-wayvalves 224 a through 224 g may also be included to allow fluid flow tobe directed between two different end points (or be received from one oftwo sources).

The cartridge 202 may also include, for example, an indicator chamber226 and a waste reservoir 248, as well as a mixing chamber 236, a firstactivation cell 242 (indicated by outlet port), a second activation cell244 (indicated by outlet port), and an optical measurement chamber 246(indicated by outlet port). The mixing chamber may have inlet ports fora short siphon 238, a long siphon 240, and a pressurization port 272.

FIGS. 33 and 34 depict section views of the mixing chamber 236. As canbe seen, the long siphon 240 extends nearly all the way to the bottom ofthe mixing chamber 236, thereby allowing fluids to be delivered to themixing chamber 236 and completely removed from the mixing chamber 236.The mixing chamber 236 also includes a short siphon 238 that may also beused to introduce fluids to the mixing chamber, if desired, but whichmay only be used to extract fluids above a predefined level from themixing chamber, i.e., the short siphon 238 cannot be used to completelyempty the mixing chamber 236 (the above discussion assumes that themixing chamber is used in the orientation depicted with respect to thefigure, with the ports located uppermost). The length of the shortsiphon 238 may be selected such that the end of the short siphon 238 isjust above the level at which the THC adduct may be located afterseparation of the solvent, indicator, THC adduct, buffer, and sample hasoccurred. Since the amounts of each substance other than the THC adductare generally known quantities, the length of the short siphon 238 canbe set once for a given analysis protocol and then left alone.

FIG. 35 depicts a section view of the optical measurement chamber 246.The optical measurement chamber 246 may be provided, for example, by acuvette or other optically clear vessel or passage that is suitable forexposing the samples contained within to excitation light andtransmitting emitted light out for detection by the optical measurementsensor 252.

FIG. 36 depicts a section view of the first activation cell 242; thesecond activation cell 244 may be similar. The first activation cell242, in this case, is a pipette that is held in a housing and that isinterfaced with an activation cell fluid port 274 and an activation cellpneumatic port 276. The activation cell fluid port 274 may be connectedto the fluid handling systems of the analysis system 200, whereas theactivation cell pneumatic port 276 may be connected to a pneumaticsystem, e.g., such as an air pump 254 (which may, in turn, be connectedwith a muffler/filter 260, if desired). The air pump 254 may also beconnectable with the pressurization port 272 of the mixing chamber, aswell as other locations, similar to the implementation shown in FIG. 1.

FIG. 37 depicts the handheld BCM (a prototype) 206. The handheld BCM 206may include a saliva trap 210, such as may be used with alcoholbreath-analyzer testing units. An example of a suitable saliva trap 210is the ULTRAP II, described in U.S. Pat. No. 4,292,978, which is sold byGuth Laboratories, Inc. The handheld BCM 206 may also include amouthpiece 208 (provided, in this case, by one end of the saliva trap210), as well as catch media 214. Catch media 214 may include a porousmedia that has a high surface area to volume ratio, and may be asgenerally described in U.S. Patent Application No. 62/337,286. Thehandheld BCM 206 may also include on-board electronics 216 that may beconfigured to monitor how much breath has been breathed through thesaliva trap 210 and catch media 214 via a pressure sensor (not shown,but see FIG. 1).

FIG. 38 is a photograph of a prototype cartridge during assembly; thisview gives some idea of the nature of the tubing connections between thecomponents. FIG. 39 is a photograph of a prototype cartridge mountedinto a prototype base station.

The analysis system discussed herein may also include one or moreprocessors, memory, and associated electronics to allow the one or moreprocessors to control the valves, actuators, optical measurement sensor,air pump, and any other controllable elements of the analysis system inorder to carry out the operations discussed herein. The memory may storecomputer-executable instructions for controlling the one or moreprocessors to cause such operations to occur. It is to be understoodthat the present disclosure relates not only to system and apparatusimplementations of the analysis system discussed herein, but also totechniques, methods, and processes for using such analysis systems, aswell as to embodiments in which computer-executable instructions forcontrolling a processor or processors to cause such techniques to bepracticed are stored on some form of computer-readable media, e.g.,non-transitory, computer-readable media such as a hard disk, solid statedrive, or non-volatile flash memory.

In some instances, the one or more processors and memory may include atleast one processor and memory that are part of the BCM 106 and/or thecartridge 102 and/or the base station 104. In such cases, there may beprocessors and memory distributed between two or more of suchcomponents, and the components may communicate with one another, eitherthrough a wireless communications interface or a wired connection. Insome implementations, one or more of the above components may also havea wireless communications interface, e.g., a cellular interface, thatallows the one or more processors to wirelessly communicate informationto a remote device, e.g., a server. For example, the BCM 106 may includea wireless interface that may transmit information relating to a sample,including, for example, metrics regarding the volume of exhaled breath,the time taken to obtain the sample, the time that the sample wasobtained, the location where the sample was obtained (as either enteredmanually by a user or as obtained automatically, e.g., through use of aGPS receiver located in the BCM 106 or in another nearby piece ofequipment, such as a paired smartphone or police car, and/or a pictureof the subject providing the sample, e.g., as taken by a pairedsmartphone or by a camera that may be built in to the BCM 106. The samewireless communications interface, or a different wirelesscommunications interface, may also communicate test results from theanalysis system 100 to the same remote device in association with suchinformation or in association with a record identifier linking suchfurther information to previously transmitted information, allowing testresults to be associated with a particular subject and samplingtime/location.

In one embodiment consistent with the discussion provided above withrespect to FIGS. 1 through 25 and FIGS. 27 through 38, the followingquantities and compositions of chemicals may be used (the table below iswith reference to the quantities and compositions present prior toanalysis):

Reservoir/ Chamber Composition Amount Sample Ethanol (EtOH)  250 μLFirst EtOH + Buffer 750 μL (250 μL EtOH + Calibration 500 μL Buffer)Sample Second EtOH + THC + 750 μL (250 μL EtOH + Calibration Buffer 500μL Buffer + THC) Sample Buffer NaHCO₃ + Na₂CO₃ 500 μL @ 20 mM NaHCO₃ and13 mM Na₂CO₃ Solvent Methyl tertiary 3000 μL (2250 μL Heptane + butylether (MTBE) + 750 μL MTBE) Heptane Indicator Solvent Hydrochloric acid1500 μL (HCl, 100 μM concentration) Indicator Rhodamine +   1 mg Chambercamphorsulfonic acid + sodium nitrite Cleaning Agent Acetonitrile or7500 μL EtOH

In such an embodiment, each of the three samples (the breath constituentsample and the two calibration samples) will be approximately 750 μLprior to the addition of the liquid indicator; the two calibrationsamples start out at approximately 750 μL (the second calibration samplemay be slightly larger in volume due to the additional presence of THC,although this is a negligible contributor to overall volume in view ofthe other volumes used), and the sample volume may be brought up to 750μL after the elution is completed and the buffer is added to the elutedsample. After the buffer has been added to each sample, if not alreadypresent, 250 μL of liquid indicator may be added to each sample,bringing the overall sample volumes each to 1000 μL. Each combinedindicator and sample may then be combined/mixed with 1000 μL of solvent(MTBE+Heptane), and the mixture allowed to separate out. Once separationis complete (or sufficiently complete), approximately 650 μL of thetopmost separation layer may be extracted, e.g., by the short siphon,from each sample, activated, if necessary, and then subjected to opticalmeasurement to determine the amount of THC adduct that is present ineach sample.

It is to be understood that the above-described system may beimplemented in a number of different ways, and that such differentimplementations are also considered within the scope of this disclosure.For example, calibration samples are used in the example system toprovide baseline measurements that may be used to calibrate the unknownsample THC adduct measurement against THC adduct measurements obtainedfrom known quantities of THC. However, such calibration samples (and theequipment for processing them) may be omitted in some cases, e.g., ifthe accuracy of the THC measurement is not of particular concern (suchmay be the case where any non-zero amount of THC in a person's breathmay be considered to be sufficient grounds for prosecution under a“driving under the influence” statute—the exact amount may beimmaterial). Furthermore, the use of a mixing chamber may, in someinstances, be optional. For example, mixing may occur in other chambersor vessels of the analysis system instead, such as in the opticalmeasurement chamber—the mixture may be reciprocated in and out of theoptical measurement chamber repeatedly, and then allowed to separatewithin the optical measurement chamber. The optical measurement sensormay, in such implementations, be positioned such that the opticallysensitive area of the sensor is aligned with a region of the opticalmeasurement chamber where the THC adduct is expected to separate into alayer, thereby allowing the amount of the THC adduct present to bequantified. In yet further or additional implementations, the activationcells that are used may be omitted and other systems or techniques foractivating the fluorophores in the THC adduct may be used. For example,the solution containing the THC adduct may be subjected to a lightsource of a particular wavelength, an electrical charge, or some otherstimulus in order to activate the fluorophore. In the example discussedearlier in this disclosure, the activation of the fluorophores in theTHC adduct is achieved by passing the THC adduct into a particular brandand model of pipette that was found, via experimentation, to activatethe THC adduct, and then removing the activated THC adduct from thepipette. It will be appreciated that the functionality of thecalibration cell may be integrated into other components, such as theoptical measurement chamber, thereby obviating the need for a separateactivation cell (or cells). For example, if the THC adduct is an adductthat can be activated by passing an electrical charge through it, thenelectrodes may be placed so as to come into contact with the THC adductto allow such a charge to be delivered. By way of further example, suchelectrodes may be placed in the optical measurement chamber so that theTHC adduct may be activated within the optical measurement chamber; theoptical measurement chamber, in this sense, may be viewed as both theoptical measurement chamber and the activation cell. If the activationof the THC adduct involves re-usable components, such as non-consumableelectrodes, then separate activation cells for each sample to beactivated may be avoided as well, and a single, common activation cellmay be used.

It is also to be recognized that the various connections betweenreservoirs and other components may be made, for example, by way ofintegrated flow paths in a block of material, e.g., flow paths that aremachined or cast in a block of material, thereby eliminating some or allof the tubing connections that are depicted in the photographs. It isalso to be understood that the system that is discussed may potentiallybe implemented on a smaller scale, and that the apparatus depicted inthe photographs is a test prototype that uses many off-the-shelf parts,such as valves, fittings, reservoirs, etc., and may be refined to bemore compact. In such cases, the amounts of the reactants and fluidsused may be adjusted to accommodate potentially smaller sample sizes andworking volumes. Such refined versions of the apparatus are alsoconsidered to be within the scope of this disclosure.

1. A tetrahydrocannabinol (THC) detection system comprising: a firstreservoir configured to receive a breath constituent sample; a secondreservoir containing a first, non-zero amount of THC, a chambercontaining an indicator; measurement chamber; and a plurality of valvesand one or more pumps that are configured to control fluid flow from orto, the first reservoir, the second reservoir, the chamber, and themeasurement chamber, wherein the plurality of valves and the one or morepumps are arranged such that fluid flow between the first reservoir, thesecond reservoir, the chamber, the measurement chamber, the plurality ofvalves, and the one or more pumps is controllable to: a) permit thebreath constituent sample to be collected in the first reservoir; b)cause a first portion of the indicator to be flowed from the chamber andinto the first reservoir so as to mix with the breath constituent sampleto form a first amount of adduct with THC that is present in the breathconstituent sample; c) cause a second portion of the indicator to beflowed from the chamber to the second reservoir so as to mix with thefirst amount of THC in the second reservoir to form a second amount ofadduct; d) cause the second amount of the adduct to be flowed into themeasurement chamber from the second reservoir; and e) cause the firstamount of the adduct to be flowed into the measurement chamber from thefirst reservoir.
 2. The THC detection system of claim 1, wherein theindicator comprises a diazotized fluorophore.
 3. The THC detectionsystem of claim 1, wherein the indicator comprises rhodamine.
 4. The THCdetection system of claim 3, wherein the indicator comprises rhodamine123.
 5. The THC detection system of claim 1, further comprising a thirdreservoir containing a second amount of THC lower than the first amountof THC, wherein the plurality of valves and the one or more pumps arefurther arranged such that fluid flow between the first reservoir, thesecond reservoir, the third reservoir, the chamber, the measurementchamber, the plurality of valves, and the one or more pumps is furthercontrollable to: f) cause a third portion of the indicator to be flowedfrom the chamber to the third reservoir so as to mix with THC in thethird reservoir to form a third amount of adduct, and g) cause the thirdamount of the adduct to be flowed into the measurement chamber from thethird reservoir.
 6. The THC detection system of claim 5, wherein thesecond amount of THC is a zero amount of THC.
 7. The THC detectionsystem of claim 1, further comprising a waste reservoir, wherein theplurality of valves and the one or more pumps are further arranged suchthat fluid flow between the first reservoir, the second reservoir, thewaste reservoir, the chamber, the measurement chamber, the plurality ofvalves, and the one or more pumps is further controllable to: cause thesecond amount of the adduct, if any, present in the measurement chamberto be flowed into the waste reservoir prior to flowing the first amountof the adduct into the measurement chamber, and cause the first amountof the adduct, if any, present in the measurement chamber to be flowedinto the waste reservoir prior to flowing the second amount of theadduct into the measurement chamber.
 8. The THC detection system ofclaim 1, further comprising a cleaning agent reservoir containing acleaning agent, wherein the plurality of valves and the one or morepumps are further configured to control fluid flow from the cleaningagent reservoir and the plurality of valves and the one or more pumpsare further arranged such that fluid flow between the cleaning agentreservoir and the measurement chamber is controllable to: cause thecleaning agent to flow through the measurement chamber in between (e),(f), and (g).
 9. The THC detection system of claim 1, furthercomprising: a controller including: one or more processors, and amemory, wherein: the one or more processors are operatively connectedwith the memory, the valves in the plurality of valves, and the one ormore pumps, and the memory stores computer-executable instructions forcontrolling the one or more processors to: receive an indication that ananalysis is to be performed on a breath constituent in the firstreservoir; and control, responsive to receiving the indication, theplurality of valves and the one or more pumps to cause:  the firstportion of the indicator to be flowed from the chamber and into thefirst reservoir so as to combine with the breath constituent sample toform the first amount of the adduct with THC that is present in thebreath constituent sample,  the second portion of the indicator to beflowed from the chamber to the second reservoir so as to mix with thefirst amount of THC in the second reservoir to form the second amount ofthe adduct;  the second amount of the adduct to be flowed into themeasurement chamber from the second reservoir; and  the first amount ofthe adduct to be flowed into the measurement chamber from the firstreservoir.
 10. The THC detection system of claim 9, wherein the memorystores further computer-executable instructions for further controllingthe one or more processors to control the plurality of valves and theone or more pumps to cause the first amount of the adduct to be flowedinto the measurement chamber from the first reservoir before the secondamount of the adduct is caused to be flowed into the measurement chamberfrom the second reservoir.
 11. The THC detection system of claim 9,further comprising an optical measurement sensor configured to obtainoptical measurements from substances in the measurement chamber, whereinthe memory stores further computer-executable instructions for furthercontrolling the one or more processors to: cause the optical measurementsensor to obtain a first optical measurement from the measurementchamber while the first amount of the adduct is in the measurementchamber, and cause the optical measurement sensor to obtain a secondoptical measurement from the measurement chamber while the second amountof the adduct is in the measurement chamber.
 12. The THC detectionsystem of claim 9, further comprising one or more activation cells, eachcontaining a reagent that is reactive with the first amount of theadduct and the second amount of the adduct to produce products capableof emitting light, wherein the memory stores further computer-executableinstructions for further controlling the one or more processors tocontrol the plurality of valves and the one or more pumps to: cause thefirst amount of the adduct to mix with the reagent prior to flowing thefirst amount of the adduct into the measurement chamber, and cause thesecond amount of the adduct to mix with the reagent prior to flowing thesecond amount of the adduct into the measurement chamber.
 13. The THCdetection system of claim 1, wherein the first reservoir, the secondreservoir, the chamber, the measurement chamber, and the plurality ofvalves are located in a common cartridge that is configured to beinserted into an analysis unit having an optical measurement sensorconfigured to obtain luminescence readings from contents of themeasurement chamber.
 14. The THC detection system of claim 13, furthercomprising the analysis unit, wherein: the analysis unit is configuredto receive the common cartridge, the analysis unit includes the opticalmeasurement sensor.
 15. The THC detection system of claim 1, furthercomprising an indicator solvent reservoir containing an indicatorsolvent, wherein: the chamber includes a granular or powder indicator,and the plurality of valves and the one or more pumps are furtherarranged such that fluid flow between such components is controllable tocause the indicator solvent in the indicator solvent reservoir to bedelivered to the chamber in order to mix the indicator solvent with thegranular or powder indicator prior to flowing the indicator into thefirst reservoir and the second reservoir.
 16. The THC detection systemof claim 15, wherein the granular or powder indicator includes afunctionalized fluorophore.
 17. The THC detection system of claim 16,wherein the functionalized fluorophore is a rhodamine.
 18. The THCdetection system of claim 17, wherein the functionalized fluorophore isrhodamine
 123. 19. The THC detection system of claim 15, wherein theindicator solvent is hydrochloric acid.
 20. The THC detection system ofclaim 15, wherein the indicator is a diazo-functionalized reactant.